Functional impairment of p73 and p51, the p53-related proteins, by the human T-cell leukemia virus type 1 Tax oncoprotein

We have previously demonstrated that the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein represses the trans-activation function of p53 tu mor suppressor protein. Recently, several proteins with sequence homology t o p53 have been identified. In this study, we demonstrated that Tax repress es the transactivation functions of p73 alpha, p73 beta, and p51A, the p53- related proteins, as well as p53, Moreover, a mutant Tax of coactivator CBP -binding site (K88A), which activated NF-kappa B but not CREB pathway, coul d not repress the p73 nor p51 trans-activation functions, indicating that C BP-binding domain of Tax is essential for the suppression of their function s. Using proteins of Gal4-fused N-terminal region of p73 and p51, we showed that Tax-mediated inactivation of p73 or p51 requires for their N-terminal trans-activation domains. Furthermore, only the putative N-terminal trans- activation domains of them did not have enough transcriptional activities a nd their adjacent regions are essential for their full transactivation, sug gesting the existence of their second transactivation subdomains. Thus, HTL V-1 Tax inactivated the p53-related proteins through their N-terminal trans activation domains.